Patients on maintenance antipsychotic treatment may not require more than 5 mg of risperidone daily (or equivalent) to keep their risk of schizophrenia relapse low, according to a meta-analysis published in JAMA Psychiatry. Doses higher than this amount may provide a little additional protection but also cause more adverse events.
“Because patients often need to use antipsychotics for many years, adverse events, such as movement disorders and weight gain, can accumulate and result in even more severe problems, such as tardive dyskinesia or cardiovascular problems,” wrote Stefan Leucht, M.D., of the Technical University of Munich and colleagues. “Therefore, psychiatrists need to know which doses are sufficient for maintenance treatment. If lower doses than needed for short-term treatment were sufficient, the adverse-event burden could be substantially reduced.”
Leucht and colleagues combined data from 26 placebo-controlled studies that assessed relapse prevention of antipsychotics. The collected sample encompassed 4,776 patients and the following medications: oral and LAI aripiprazole, fluphenazine LAI, oral and LAI haloperidol, oral lurasidone, oral and LAI olanzapine, paliperidone LAI, oral quetiapine, risperidone LAI, oral ziprasidone, and oral zotepine. To maintain consistency, all antipsychotic doses were converted to their equivalent dose of oral risperidone.
Overall, the effectiveness of antipsychotics increased sharply at lower doses but then began to plateau. Sixty-seven percent of patients who took placebo relapsed, compared with 42% of patients taking 2.5 mg risperidone equivalents daily, 29% of patients at 5 mg daily, 25% at 7.5 mg daily, and 22% at 10 mg daily. Meanwhile, the risk of adverse side effects rose linearly with dose. For example, the dropout rate due to side effects was 4% with placebo, 4.7% at 2.5 mg risperidone equivalent daily, 5.5% at 5 mg daily, 6.5% at 7.5 mg daily, and 7.7% at 10 mg daily.
Based on this risk-benefit data, Leucht and colleagues calculated that a maintenance dose equivalent to 5 mg risperidone daily was optimal. Among patients taking potent first-generation antipsychotics such as haloperidol or fluphenazine, the optimal level was 3 mg daily, while for patients who had achieved full remission of symptoms, the optimal level was 2.5 mg daily. For comparison, risperidone is typically dosed between 4 mg to 16 mg daily for management of acute symptoms.
“The results of our meta-analysis may provide some guidance based on average patients with chronic disease. The dose-response associations in specific populations are likely to be different,” Leucht and colleagues noted. “For example, doses might be lower for patients with a first episode of schizophrenia and higher for treatment-resistant patients. Moreover, the substantial interindividual variability in all these outcomes is important to consider. Individual dosing decisions should be guided by patient wishes. For many patients, adverse events may be a priority, and for many others, avoidance of relapse may be more important.”
For related information, see the Psychiatric News article “What Antipsychotic Dose Is Most Effective?”
(Image: iStock/Olivier Le Moal)
